The cornea is a transparent tissue without blood vessels on the front surface of an eyeball, which is often called the dark part of an eye. More particularly, the cornea protects the eye from external conditions, and plays a significant role of refracting and transmitting lights to get a sight of objects. It has well-developed nerve fibers to sensitively respond to foreign substances. The cornea is composed of five layers including a corneal epithelium, Bowman's membrane, corneal stroma, Descemet's membrane and corneal endothelium.
The surface of the cornea is directly exposed to the outside and vulnerable to wound or scratch. Therefore, corneal injuries often occur in patients suffering from ophthalmic diseases such as dry eye syndrome because a shortage of tear drastically deteriorates eyeball protection function of tears. The corneal injuries may cause symptoms such as a feeling of stimulus, a feeling of irritation or dryness and, lead to corneitis when getting worse. Therefore, in order to keep the eyeball healthy and preserve the eyesight, it is necessary to prevent the cornea from being injured, prevent trivial corneal injuries from being worse or treat the injured cornea.
Meanwhile, it is well known that, when the cornea is injured, in particular, by alkali burns, broad infiltration of polymorphonuclear leukocytes (PMN) occurs (Invest. Ophthalmology & Vis. Sci., 1987, 28, pp. 295-304). Such PMN infiltration is part of general inflammatory responses in association with tissue injury. However, in case of the chemical burns of the cornea, PMN infiltration is not only a primary inflammatory response but also leads to ulcer, or may even cause corneal perforation (Trans. Am. Acad. Ophthalmol. Otolaryngol., 1970, 74. pp. 375-383, Invest. Ophthalmology & Vis. Sci., 1979, 18, pp. 570-587). In fact, PMN is known as a major source of collagenase to destroy corneal collagen tissues. Therefore, it is understood that expansion of lesions is stopped by preventing infiltration of PMN, and that the progress of a corneal injury to ulcer may be delayed by inhibiting PMN metabolism. A number of studies have reported that citric acid is effective in reducing PMN infiltration (Exp. Eye. Res., 1984, 39, pp. 701-708).
Meanwhile, thymosin β4 is a protein first discovered in the thymus gland in 1981, which comprises 41 to 43 amino acids and has an isoelectric point of 5.1. In 1991, thymosin β4 was identified by Liva et al. as an actin-sequestering molecule from animal cells, and thereafter, found to be involved in the immune regulation and neuro-endocrine system. Recently, Korean Laid-open Patent Publication No. 10-2008-33939 discloses an eye drop composition comprising thymosin β4 and an amino acid stabilizer, which may further comprise a bulking agent, a buffer and a pH modifier. However, this publication does not describe any desired combination and contents of individual components to optimize or enhance the efficacy of thymosin β4.
As a result of extensive efforts to find out an optimum combination and contents of components, the present inventors have found that a specific organic acid may influence upon the activity of thymosin β4 and a composition containing acid could be used for treating corneal injuries, thereby accomplishing the present invention.